KR101854807B1 - Unmanned automatic cell culture system - Google Patents

Abstract

The present invention relates to an automated unmanned cell culture system comprising an incubator for receiving a plurality of flasks for cell culture, a microscope for observing the culture condition of the cells in the flask, A solution reservoir for storing a plurality of solutions required for cell culture, a solution reservoir for storing a plurality of solutions required for cell culture, a solution reservoir for supplying the solution to the flask, the incubator, the microscope, , A tube table for placing at least one conical tube capable of receiving the solution necessary for cell and cell culture, a tube table for accommodating the conical tube, and a solution for cell and cell culture in the conical tube Centrifugation to perform centrifugation for A gripper for transferring the conical tube between the work table, the tube table and the centrifugal separator, a pipette for injecting or collecting cells and a solution necessary for cell culture into the flask or the conical tube, And a controller for controlling operations of the gripper and the pipette.

Description

UNMANNED AUTOMATIC CELL CULTURE SYSTEM [0002]

The present invention relates to an automated, automated cell culture system capable of automatically culturing and dispensing cells.

Cell culture generally means aseptically removing tissue from an individual of multicellular organisms, culturing and propagating in a vessel. In recent years, in the field of cell culture and the field of regenerative medicine, there has been a demand for a technique for obtaining a cell product that can be used for a biological preparation or the like and a cell itself to be used for constructing a regenerated tissue, by stably cultivating a large amount of cells for a long period of time automatically and stably.

Conventionally, a cell culture operation is performed by manually transporting and manipulating a flask in which a cell is cultured by an operator in a laboratory. However, the cell cultivation work by humans involves a large variation in productivity depending on the skill of the operator, and the entire process must be discarded due to human errors such as a time for replacing the culture medium or a time for dispensing the cells, . In addition, since a skilled worker of a high wage must perform a predetermined process repeatedly at a predetermined time, there is a problem that a labor cost is large and a manufacturing cost is difficult to be reduced as a result.

The background technology of the present invention is disclosed in Korean Patent Laid-Open Publication No. 10-2015-0006422 (published on Jan. 16, 2015).

It is an object of the present invention to provide an unmanned automated cell culture system capable of automatically cultivating and dispensing cells.

It is another object of the present invention to provide an automated unmanned cell culture system capable of controlling the injection of a culture solution optimized based on a cell culture state upon cell division.

In addition, the present invention aims to provide an automated unmanned cell culture system capable of selectively designing a combination of processing modules necessary for a process through an efficient logistics configuration and process processing and modular design.

It is also an object of the present invention to provide an automated cell culture incubator capable of managing a cell culture flask.

It is also an object of the present invention to provide a cell culture incubator that provides a transport environment for a flask to be automatically moved by a robot in a limited incubator space.

It is to be understood, however, that the technical scope of the present invention is not limited to the above-described technical problems, and other technical problems may exist.

As a technical means for accomplishing the above technical object, the automated unmanned culture system according to one embodiment of the present invention includes an incubator for accommodating a plurality of flasks for cell culture in multiple layers, a culture of cells in the flask A microscope for observing the state of the flask, a workbench capable of placing the flask therein, a workbench for putting the solution into the flask for cell culture, sampling and transporting the sample from the flask, a plurality of solutions required for cell culture A flask handling robot for transferring the flask between the microscope and the workbench; a tube table for placing at least one conical tube capable of receiving the solution necessary for cell and cell culture; And the cells and cells in the conical tube A gripper for transferring the conical tube between the work table, the tube table and the centrifugal separator; and a cell and cell culture for the flask or the conical tube. And a controller for controlling operations of the flask handling robot, the gripper, and the pipette.

According to one embodiment of the present invention, the flask handling robot transfers a first flask containing raw material cells from the incubator to the work table, and the pipette separates a first solution for cell separation from the solution reservoir into the first And the flask handling robot shakes the first flask into which the first solution has been injected, the pipette removes the first solution from the first flask, and the pipette removes the second solution for cell separation Is injected from the solution reservoir into the first flask and the flask handling robot transfers the first flask into which the second solution has been injected to the incubator so that the raw material cells in the first flask are supplied to the incubator for a predetermined time, And the flask handling robot receives the first Wherein the pipette transports the cell culture medium from the solution reservoir to the first flask and the gripper transfers the first conical tube from the tube table to the work table, A sample containing the material cells is collected from the first flask into which the cell culture medium is injected, and is injected into the first conical tube. The gripper transfers the first conical tube to the centrifuge, Centrifugation is performed on the specimen in the conical tube, the gripper transfers the first conical tube from the centrifuge to the work table, the pipette removes the upper layer current fluid from the first conical tube, Injects the cell culture medium from the solution reservoir into the first conical tube, The handling robot transfers the second flask, the third flask and the fourth flask from the incubator to the work table, and the pipette injects the cell culture medium from the solution reservoir into the second flask, the third flask and the fourth flask And the pipette uniformly injects the cell suspension liquid containing the raw material cells from the first conical tube subjected to centrifugal separation into the second flask, the third flask and the fourth flask, The second flask, the third flask and the fourth flask containing the cell suspension liquid may be transferred to the incubator.

According to an embodiment of the present invention, the pipette collects a specimen of the cell suspensions containing the raw material cells from the first conical tube subjected to centrifugal separation, and injects the specimen into a second conical tube, Wherein the third solution for cell staining is injected into a 2-conical tube, and the unmanned automated cell culture system further comprises a cell number measuring device for measuring the cell number in the specimen, The cell count was measured with respect to the specimen in the second conical tube, and the pipette was used to inject the cell culture medium from the solution reservoir into the second flask, the third flask and the fourth flask, The cell culture medium can be injected on the basis of the measured cell number.

According to one embodiment of the present invention, the pipette further injects a cell suspension liquid into the first conical tube subjected to centrifugal separation, and the pipette collects the specimen into which the cell suspension liquid is further injected, It can be injected into 2 conical tubes.

According to one embodiment of the present invention, the incubator includes a housing, a first door provided on a front surface of the housing, a second door provided on a rear surface of the housing opposite to the front surface of the housing, A tray capable of stacking a plurality of flasks for cell culture and a driving unit positioned outside the housing and coupled to the tray to rotate the tray.

According to an embodiment of the present invention, the tray includes a plurality of plates arranged at equal intervals in the vertical direction, an upper cover plate disposed on the uppermost plate of the plurality of plates, And a lower cover plate disposed on the lower side, wherein each of the plurality of plates is formed in a circular shape and the plurality of flasks can be placed at regular intervals.

According to an embodiment of the present invention, the plurality of plates, the upper cover plate, and the lower cover plate each include eight coupling grooves located at equal intervals, and the tray includes the plurality of plates, And eight connecting rods passing through the eight connecting grooves of the lower cover plate in the vertical direction to connect the plurality of plates, the upper cover plate and the lower cover plate.

According to an embodiment of the present invention, the driving unit is located on the upper side of the housing and may be coupled to the center of the upper cover plate.

According to one embodiment of the present invention, the plurality of plates include a ring-shaped first sub-plate, a ring-shaped second sub-plate having a diameter smaller than the diameter of the first sub-plate and concentric with the first sub- A plurality of connecting portions connecting the first sub-plate and the second sub-plate, and a plurality of guides positioned equidistantly on the upper surface of the first sub-plate and guiding the placement position of the flask, Through the second sub-plate of the plate of the flask to guide the placement position of the flask.

According to an embodiment of the present invention, the plurality of plates may further include a plurality of reinforcing portions extending from the connecting portion in the downward direction of the incubator to prevent warping of the plate.

According to an embodiment of the present invention, the size of the second door is smaller than the size of the first door, the first door is openable and closable by a user, the second door is automatically opened and closed, The flask can be carried by the flask handling robot to the inside and outside of the housing.

The above-described task solution is merely exemplary and should not be construed as limiting the present disclosure. In addition to the exemplary embodiments described above, there may be additional embodiments described in the drawings and detailed description of the invention

According to the above-mentioned problem solving means of the present invention, it is possible to provide an unmanned automated cell culture system capable of automatically culturing and dispensing cells.

Further, the present invention can provide an unmanned automated cell culture system capable of controlling the injection of a culture medium optimized based on the cell culture state upon cell division.

In addition, the present invention enables efficient placement of the flask by a circular plate that stacks the cell culture flasks in multiple layers.

In addition, the present invention provides a cell culture incubator in which cell culture flasks are stacked in multiple layers, a flask handling robot approaches a rotatable tray, and a transportation environment is automatically provided so that the flask can be moved, can do.

Further, the present application can improve the stacking and transport efficiency of a plurality of flasks in a limited incubator space by stacking cell culture flasks in multiple layers and rotating them.

The effects obtainable herein are not limited to the effects mentioned above, and other effects not mentioned can be clearly understood by those skilled in the art from the following description .

1 is a schematic view of an automated cell culture system according to an embodiment of the present invention.
FIG. 2 is a flowchart illustrating a method of automated cell culture using unmanned automated cell culture system according to an embodiment of the present invention.
FIG. 3 is a schematic view of a cell culture incubator that can be included in an automated cell culture system according to an embodiment of the present invention.
FIG. 4 is a view schematically showing a configuration of a cell culture incubator according to an embodiment of the present invention.
FIG. 5 is a perspective view illustrating the inside of a cell culture incubator according to an embodiment of the present invention. FIG.
6 is a view showing a configuration of a tray according to an embodiment of the present invention.
7 is a view showing a configuration of a plate according to an embodiment of the present invention.
FIG. 8 is a view illustrating an embodiment in which a flask is transported by a flask handling robot according to an embodiment of the present invention.

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings so that those skilled in the art can easily carry out the present invention. It should be understood, however, that the present invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein. In the drawings, the same reference numbers are used throughout the specification to refer to the same or like parts.

Throughout this specification, when a part is referred to as being "connected" to another part, it is not limited to a case where it is "directly connected" but also includes the case where it is "electrically connected" do.

It is to be understood that throughout the present application, when a member is located on another member "on top," "on top," "under," "bottom," or the like, And the case where another member exists between the two members.

Throughout this specification, when an element is referred to as "including " an element, it is understood that the element may include other elements as well, without departing from the other elements unless specifically stated otherwise.

1 is a schematic view of an automated cell culture system according to an embodiment of the present invention.

1, an unmanned automated cell culture system includes an incubator 100, a microscope 201, a solution reservoir 202, a centrifuge 203, a work table 210, a flask handling robot 220, a tube table 230 A gripper 240, a pipette 250, a control unit 260, and a cell counting unit 270. The automated unmanned cell culture system according to an embodiment of the present invention may include at least a part of the various configurations in the form of a module.

The incubator 100 can accommodate a plurality of flasks for cell culture. The flask accommodated in the incubator 100 can be transferred to the microscope 201 by the flask handling robot 220 and the cell culture condition in the flask can be observed through the microscope 201. [

The work table 210 is capable of placing the flask and can provide a working environment for injecting the solution into the flask for cell culture. Also, sample collection and transfer operations from the flask can be performed on the work table 210.

The solution reservoir 202 may store a plurality of solutions required for cell culture. The solution reservoir 202 may include, for example, a cell culture medium, PBS (Phosphate Buffer Saline), Trypsin, Trypan Blue, and the like. For example, the solution reservoir 202 may have both functions of cooling / warming. When the solution is stored, the solution temperature is maintained at about 4 degrees Celsius, and when the solution is used, about 37 degrees Celsius The solution temperature can be improved.

The flask handling robot 220 can transfer the flask between the incubator 100, the microscope 201 and the work platform 210. The flask handling robot 220 can transport the flask placed in the incubator 100 to the inside and the outside of the incubator 100.

According to one embodiment of the present invention, the flask handling robot 220 may include an arm including a plurality of joints, and the flask mounted on the incubator 100 may be selectively gripped and carried.

The tube table 230 can accommodate at least one conical tube capable of receiving the solution needed for cell and cell culture. By way of example, a conical tube can hold a solution that is necessary for cell and cell culture at a volume of 50 ml.

The centrifuge 203 can accommodate the conical tube and perform centrifugation on the cells and cells in the conical tube and the solution required for cell culture.

A gripper 240 can transfer the conical tube between the work table 210, the tube table 230 and the centrifuge 203. According to one embodiment of the present disclosure, the gripper 240 may include a plurality of arms and may selectively carry and carry the conical tube.

The pipette 250 may be injected or harvested with the solution necessary for cell and cell culture on a flask or conical tube. The pipette 250 may include a syringe for injecting or collecting the solution. For example, the pipette 250 may include an Air Displacement Pipette (ADP) module that automatically supplies a volume of liquid sample to a designated location.

The cell counter 270 can measure the number of cells in a specimen contained in a conical tube or flask. For example, the cell counting device 270 can count the number of cells by capturing and analyzing an image of a specimen.

The control unit 260 may control the operations of the flask handling robot 220, the gripper 240, the pipette 250, and the cell counter 270.

In FIG. 1, the gripper 240, the pipette 250, the control unit 260, and the cell counting unit 270 are shown as simple blocks for clarity of explanation, And can be combined.

Hereinafter, the operation of the automated unmanned cell culture system according to one embodiment of the present invention will be described.

The flask handling robot 220 can transfer the first flask containing the raw material cells from the incubator 100 to the work table 210. The first flask may contain a cell culture medium for preserving and culturing the cells for the source material. For example, the incubator 100 can accommodate 64 flasks, and can accommodate the first flasks containing raw material cells and empty 63 flasks.

According to one embodiment of the invention, the flask handling robot 220 can transfer the first flask to the microscope 201 before transferring it to the workbench 210. The state of the cells in the first flask can be confirmed through the microscope 201. According to one embodiment of the present invention, when the cells contained in the first flask are determined to be dead or incapable of culturing, the flask handling robot 220 may discard the first flask.

The flask handling robot 220 can transfer the first flask to the workbench 210 that has been found to be in good condition.

According to another embodiment of the invention, the gripper 240 can transfer the conical tube from the tube table 230 to the work table 210. The pipette 250 can sample a cell sample from the first flask transferred to the work table 210 and inject it into a conical tube. The gripper 240 may transfer the conical tube containing the cell sample to the tube table 230 and the pipette 250 may discard the cell culture medium contained in the first flask. The conical tube moved to the tube table 230 can be confirmed by the user or the control unit 260 through the microscope provided in the tube table 230. Illustratively, the flask handling robot 220 may discard the first flask if the cells contained in the conical tube are killed by the user or the control unit 260, or if it is determined that the culture is impossible.

The pipette 250 can collect a predetermined amount of the first solution for cell separation from the solution reservoir 202. In addition, the first solution may be injected into the first flask delivered to the work table 210. The first solution may be, for example, a PBS solution to facilitate cell separation.

The flask handling robot 220 may shake the first flask so that the first solution injected into the first flask can react with the cells. Further, after a lapse of a predetermined time, the pipette 250 can remove the first solution from the first flask.

Next, the pipette 250 can inject a second solution for cell separation from the solution reservoir 202 into the first flask. The second solution may be, for example, a trypsin solution.

The flask handling robot 220 may transfer the first flask into which the second solution has been injected to the incubator 100 so that the cells for raw materials in the first flask may be cultured in the incubator 100 for a predetermined time. The first flask may be incubated in the inspector 100 in reaction with the second solution. The predetermined time may be, for example, 3 minutes to 5 minutes, but is not limited thereto.

The flask handling robot 220 can transfer the first flask cultured for a predetermined time from the incubator 100 to the work table 210. [ Further, the pipette 250 can inject the cell culture medium collected from the solution reservoir 202 into the first flask.

The gripper 240 transfers the first conical tube from the tube table 202 to the work table 210 and the pipette 250 collects the sample containing the raw material cells from the first flask into which the cell culture medium is injected It can be injected into a conical tube. The first flask in which the sample is collected may be discarded by the flask handling robot 220.

The gripper 240 can transfer the first conical tube to the centrifuge 203 and the centrifuge 203 can perform centrifugation on the specimen in the first conical tube. Illustratively, the specimen in the first conical tube that has undergone centrifugation can be separated into a cell layer and a solution layer above the cell layer. The gripper 240 can transfer the centrifuged first conical tube from the centrifuge 203 to the work table 210 and the pipette 250 can remove the upper layer contaminant from the first conical tube.

Further, the pipette 250 can re-inject the cell culture medium collected from the solution reservoir 202 into the first conical tube. The cell preservation and culture environment can be maintained as the cell culture medium is re-injected into the cells from which the upper layer suspension has been removed.

The concentration of the cell diluent contained in the first conical tube which has been centrifuged by the user or by microscopy can be determined. For example, the concentration of the cell diluent may mean the concentration of the solution containing the re-injected cell culture medium relative to the cells for the raw material. When the concentration of the cell diluent in the first conical tube is higher than the predetermined concentration, that is, when the population of cells for the raw material is larger than that of the solution, the pipette 250 can further inject the cell suspension into the first conical tube. The cell suspension may be, but is not limited to, a cell culture medium.

When the concentration of the cell diluent contained in the first conical tube is less than the preset concentration, the pipette 250 can collect a sample of the cell suspensions containing the raw material cells from the first conical tube subjected to centrifugation, The collected specimen can be injected into the second conical tube. The second conical tube may be an empty tube different from the first conical tube. The pipette 250 may also be injected into the second conical tube by collecting a third solution for cell staining from the solution reservoir 202. The third solution may be a Trypan Blue solution for cell staining. The cell counting device 270 can measure the cell number of the specimen in the second conical tube into which the third solution is injected.

The flask handling robot 220 may transfer the second flask, the third flask, and the fourth flask from the incubator 100 to the workbench 210. Illustratively, the second flask, the third flask and the fourth flask may be empty flasks different from the first flask.

The pipette 250 can be taken from the cell culture medium from the solution reservoir 202 and injected into the second flask, the third flask and the fourth flask, respectively. Illustratively, the pipette 250 can determine and inject the amount of the cell culture medium based on the number of cells measured by the cell number meter 270. That is, the amount of the cell culture medium can be adjusted based on the number of cells to optimize the preservation and culture environment of the cells.

The pipette 250 can uniformly inject the cell suspension from the first conical tube subjected to the centrifugation into the second flask, the third flask and the fourth flask into which the cell culture medium is respectively injected . In addition, the flask handling robot 220 can transfer the second flask, the third flask, and the fourth flask containing the cell suspension liquid to the incubator 100. The second flask, the third flask, and the fourth flask may be incubated in the incubator 100.

FIG. 2 is a flowchart illustrating a method of automated cell culture using unmanned automated cell culture system according to an embodiment of the present invention. The automated unmanned cell culture method shown in FIG. 2 can be performed by the automated unmanned cell culture system described above with reference to FIG. Therefore, even if omitted below, the description of the unmanned automated cell culture system through FIG. 1 can be similarly applied to FIG. 2

In step S201, the flask handling robot 220 can transfer the first flask containing the raw material cells from the incubator to the work table 210, and the pipette 250 separates the first solution for cell separation into the solution reservoir 202, To the first flask. The first solution may be, for example, PBS.

In step S202, the flask handling robot 220 shakes the first flask into which the first solution is injected, the pipette 250 removes the first solution from the first flask, and the pipette 250 is moved to the second The solution can be injected from the solution reservoir 202 into the first flask. The second solution may be, for example, trypsin.

In step S203, the flask handling robot 220 can move the first flask into which the second solution has been injected to the incubator 100, and the incubator 100 can cultivate the raw material cells in the first flask for a preset time .

In step S204, the flask handling robot 220 may transfer the first flask from the incubator 100 to the work table 210 and the pipette 250 may inject the cell culture medium from the solution reservoir 202 into the first flask .

In step S205, the gripper 240 can transfer the first conical tube from the tube table 230 to the work table 210, and the pipette 250 can be moved from the first flask containing the cell culture medium Samples can be taken and injected into a first conical tube.

In step S206, the gripper 240 can transfer the first conical tube to the centrifuge 203, and the centrifuge 203 can perform centrifugation on the specimen in the first conical tube.

In step S207, the gripper 240 can transfer the first conical tube from the centrifuge 203 to the work table 210, and the pipette 250 can remove the upper layer current fluid from the first conical tube, 250 may re-inject the cell culture medium from the solution reservoir 202 into the first conical tube.

In step S208, the controller 260 can confirm the concentration of the cell diluent contained in the centrifuged first conical tube.

If the control unit 260 determines in step S209 that the first conical tube has a predetermined concentration or more, that is, if the population of the raw material cells is larger than that of the solution, the pipette 250 adds a cell suspension liquid to the first conical tube Can be injected. The cell suspension may be, but is not limited to, a cell culture medium.

If the control unit 260 determines in step S210 that the concentration of the cell diluent contained in the first conical tube is less than the predetermined concentration, the pipette 250 may extract, from the first conical tube, a sample of the cell suspensions containing the raw material cells And the collected specimen can be injected into the second conical tube. The pipette 250 can also be poured into the second conical tube by collecting a third solution for cell staining from the solution reservoir 202. The cell counter 270 can measure the cell number of the specimen in the second conical tube into which the third solution is injected.

According to one embodiment of the present invention, the pipette 250 can collect a sample of the cell suspensions containing the raw material cells from the first conical tube into which the cell suspension is injected, . In addition, in step S209, the pipette 250 can collect a specimen of the cell suspensions containing the raw material cells from the first conical tube into which the cell suspension is further injected. The collected specimen is injected into the second conical tube can do. The pipette 250 can be injected into the second conical tube by collecting a third solution for cell staining from the solution reservoir 202. The cell counter 270 can measure the cell number of the specimen in the second conical tube into which the third solution is injected.

The flask handling robot 220 can transfer the second flask, the third flask and the fourth flask from the incubator 100 to the work table 210 in step S211 and the pipette 250 can transfer the cell culture medium to the solution reservoir 202 ) Into the second flask, the third flask and the fourth flask. Illustratively, the second flask, the third flask, and the fourth flask may be empty flasks to be used for culturing cells after they are injected into cells. According to one embodiment of the present invention, in step S211, the pipette 250 can determine the amount of cell culture medium to be injected into the second flask, the third flask, and the fourth flask according to the number of cells identified in step S210 .

In step S212, the pipette 250 is centrifuged. In step S207, the cell suspension containing the raw material cells is transferred from the first conical tube into which the cell culture medium is further injected to the second, third, and fourth flasks It can be evenly injected into a flask.

In step S213, the flask handling robot 220 may transfer the second flask, the third flask, and the fourth flask containing the cell suspension liquid to the incubator 100, and the incubator 100 may transfer the second flask, the third flask, And the cells of the fourth flask can be cultured.

As described above, according to the unmanned automated cell culture system according to one embodiment of the present invention, the cultivation process of the source cells can be performed automatically.

3 is a schematic diagram of a cell culture incubator that can be included in an automated cell culture system according to one embodiment of the present invention.

3 (a), 3 (b) and 3 (c) show a perspective view of the incubator, a back view of the incubator and a cross-sectional view of the incubator, respectively.

3 (a) to 3 (c), the incubator 100 includes a housing 101, a first door 102, a second door 103, a tray 110 and a driving unit 120. [ The first door 102 may be provided on the front surface of the housing 101. The second door 103 may be provided on a rear surface of the housing 101, which faces the front surface of the housing 101. Here, the front face can refer to the 8 o'clock direction with reference to Fig. 3 (a), and the rear face can mean the 2 o'clock direction.

3 (a) and 3 (b), the first door 102 can be opened and closed by a user. The user can open the first door 102 to place the flask for culturing the cells on the tray 110 and take out the flask set to the outside of the incubator 100. [ Also, the second door 103 can be automatically opened and closed. Automatic opening and closing of the second door 103 will be described later with reference to FIG.

According to one embodiment of the present invention, the second door 103 may be formed smaller than the first door 102. The size of the second door 103 is made smaller than the size of the first door 102 so that the flask can be moved to the inside of the incubator 100 by transporting and placing the flask through the second door 103 by the flask handling robot, The homeostasis of the culture environment such as concentration, temperature, and humidity can be maintained.

Referring to FIG. 3 (c), the incubator 100 may include a tray 110 for loading a flask used for cell culture and a driving unit 120 for rotating the tray. The tray 110 is located inside the housing 101 and can stack a plurality of flasks for cell culture.

The driving unit 120 may be located outside the housing 101 and may be coupled with the tray 110 to rotate the tray 110. The tray 110 and the driving unit 120 will be described in more detail with reference to FIGS.

FIG. 4 is a view schematically showing a configuration of a cell culture incubator according to an embodiment of the present invention, and FIG. 5 is a perspective view illustrating the inside of a cell culture incubator according to an embodiment of the present invention.

4 to 5, the tray 110 may include a plurality of plates 111 arranged at even intervals in the vertical direction. According to one embodiment of the invention, each of the plurality of plates 111 is formed in a circular shape, and a plurality of flasks 10 can be placed on the plate 111 at regular intervals. According to one embodiment of the present invention, the tray 110 may include eight plates 111, and eight flasks 10 may be mounted on each plate 111.

4, the tray 110 includes an upper cover plate 112 disposed on the uppermost plate of the plurality of plates 111, and is disposed below the lowest plate of the plurality of plates 111 The lower cover plate 113 may be formed of a metal plate. The shapes of the plates 111, 112 and 113 and the placement of the flask 10 will be described later with reference to FIG.

Referring to FIG. 4, according to one embodiment of the present invention, the driving unit 120 may be positioned on the upper side of the housing 101. It may also be located below the housing 101, depending on the embodiment. The position of the driving unit 120 is not necessarily limited to the above example. By positioning the driving unit 120 on the upper side of the housing 101, there is an advantage that the maintenance can be easily performed in the future.

According to one embodiment of the present invention, the driving unit 120 may be coupled to the center of the upper cover plate 112. The driving unit 120 is coupled to the center of the upper cover plate 112, that is, the center of the tray 110 as shown in FIG. 5, and the driving unit 120 is driven to transmit power generated from the driving unit 120 The tray 110 can be rotated.

The driving unit 120 may transmit the driving force to the tray 110 through an arm connected to the tray 110 so that the tray 110 can rotate. The driving unit 120 may include various types of motors. For example, the driving unit 120 may include a servo motor or a step motor.

In addition, the incubator 100 may include a controller 130 for controlling the driving of the second door 103 and the driving unit 120. The control unit 130 can receive a control signal based on a user input from an external device interlocked with the incubator 100 and can control the driving of the driving unit 120 based on the control signal. The external device may include any type of wireless communication device, such as, for example, a computer, a notebook, a smartphone, a SmartPad, a tablet PC, and the like.

Referring to FIG. 5, the incubator 100 may include a water pan 104 in the housing 10 to receive moisture for humidity control. According to one embodiment of the present invention, the sensor unit detects the level of the liquid contained in the water pan 104, and the environment in the housing 10 can be controlled based thereon.

6 is a view showing a configuration of a tray according to an embodiment of the present invention.

FIG. 6A to FIG. 6A are views showing a first embodiment of the tray 110, and FIG. 6B is a view showing a second embodiment of the tray 110. FIG.

6A, the plurality of plates 111, the upper cover plate 112, and the lower cover plate 113 may include eight coupling grooves 114 positioned at equal intervals. Illustratively, the coupling grooves 114 included in the respective plates 111, 112, and 113 may be formed symmetrically with respect to the plates 111, 112, and 113 in the same direction when viewed from the vertical direction.

The tray 110 passes through the corresponding eight grooves 114 of the plurality of plates 111, the upper cover plate 112 and the lower cover plate 113 in the vertical direction to form a plurality of plates 111, And may include eight engagement rods 115 for coupling the plate 112 and the lower cover plate 113. As shown in Fig. 6 (a), the coupling grooves 114 of the respective plates 111, 112, and 113 are equally spaced from each other and are formed at symmetrical positions with respect to each other, The engaging rods 115 may be equidistantly spaced and vertically positioned from each plate 111, 112, 113. In the above description, the number of the coupling grooves 114 and the coupling rods 115 is eight. However, the present invention is not limited thereto.

The coupling rod 115 may include a support member 116 for fixing each of the plurality of plates 111 at a predetermined height. 6A, a plurality of support members 116 may be provided at equal intervals within the length of the coupling rod 115. As shown in FIG. In addition, the supporting members 116 provided on the respective coupling rods 115 may be provided at the same height as the supporting members 116. For example, referring to FIG. 6 (a), each of the support members 116 is provided at the same height in the different coupling rods 115, so that a plurality of plates 111 Can be horizontally positioned, and can be fixed to the coupling rods 115 at equal intervals between the plurality of plates 111.

According to one embodiment of the present invention, a coupling member 117 connected to the driving unit 120 may be provided on the upper surface of the upper cover plate 112. Illustratively, the coupling member 117 may be provided at the center of the upper cover plate 112. The coupling member 117 may be connected to the driving unit 120 in various coupling schemes. For example, it may be connected to an arm of the driving unit 120 through a screw coupling, a bolt coupling, a wedge coupling, or the like. The driving force generated in the driving unit 120 is transmitted to the tray 110 through the coupling member 117 so that the tray 110 can rotate. The connection of the coupling member 117 and the driving unit 120 is not limited to the above description.

7 is a view showing a configuration of a plate according to an embodiment of the present invention. 7 (a) is a front perspective view of the plate, and Fig. 7 (b) is a view showing an embodiment in which a flask is placed on a plate.

The following description will be made with reference to any one of the plurality of plates 111, and the plurality of plates 111 may have the same shape or configuration. 7 (a), the plate 510 includes a first sub-plate 520, a second sub-plate 530, a plurality of connection portions 540, a plurality of guides 550, 560).

Referring to FIG. 7A, the first sub-plate 520 may be formed in a ring shape. In addition, the first sub-plate 520 may include a plurality of holes formed at even intervals.

The second sub-plate 530 may have a diameter smaller than the diameter of the first sub-plate 520. Further, the first sub-plate 520 may be provided in a ring shape concentrically. The second sub-plate 530 may include a plurality of holes formed at equal intervals and eight coupling grooves 511 through which the coupling rods 115 pass. Eight coupling grooves 511 can be understood as the same concept as the eight coupling grooves 114 described in Fig.

The plurality of connection portions 540 may connect the first sub-plate 520 and the second sub-plate 530. The connection portion 540 may include a plurality of holes formed at even intervals.

As the plate 510 is formed in a circular shape, the flask 10 placed on the plate 510 can be placed at the maximum efficiency. In addition, the tray 110 including the plurality of plates 510 within the constrained space of the housing 10 by the circular plate 510 can exhibit maximum efficiency. 5, the tray 110 can be formed into a cylindrical shape by the circular plate 510, and the flask can be taken in and out only by the rotation of the tray 110 by the driving unit 120 So that the space in the housing 10 can be efficiently utilized. For example, a plurality of flasks 10 can be mounted as compared with a case where the tray 110 is formed in a rectangular shape, and the flask requiring movement of the tray 110 is rotated by the flask handling robot 220 by rotating the tray 110, The transportation of the flask handling robot 220 in the horizontal direction is unnecessary and space utilization can be maximized.

The plurality of guides 550 may be disposed at equal intervals on the upper surface of the first sub-plate 520 to guide the placement position of the flask 10. Referring to FIG. 7A, each of the plurality of guides 550 has a predetermined length and may be provided on the upper surface of the first sub-plate 520 at equal intervals between the guides 550. The flask 10 can be placed at an interval between the guide 550 and the guide 550, as shown in Fig. 7 (b).

The coupling rods 115 described above can guide the placement position of the flask 10 through the second sub-plate 530 of the plurality of plates 510. Referring to FIG. 7 (b), the eight coupling rods 115 can pass through the eight coupling grooves 511 formed in the second sub-plate 530. At this time, the flask 10 can be placed at a distance between the coupling rod 115 and the coupling rod 115.

According to one embodiment of the present invention, the guides 550 are spaced apart from one another at equal intervals, and the two guides 550, which are adjacent to each other when the coupling rods 115 are spaced apart at equal intervals, The flask 10 can be placed in a space above one connection part 540 formed by the connection part 115. The equal spacing of each of the guides 550 and the equal spacing of each of the coupling rods 115 may be different. 7B, the front end of the flask 10 (the portion facing the second sub-plate 530) is placed at a distance between the plurality of engagement rods 115, The rear ends of the flasks 10 are placed at intervals so that the plurality of flasks 10 can be guided so as to be spaced apart at regular intervals and the stability against placement during rotation by the driving unit 120 is provided to the plurality of flasks 10 can do.

7A, a plurality of reinforcing portions 560 extend from the connecting portion 540 in the downward direction of the incubator 100 to prevent the plate 510 from being warped. The load of the flask 10 mounted on the plate 510 is determined by the distance between the guides 550 of the first sub plate 520 and the distance between the connecting bars 115 of the second sub plate 530, Lt; / RTI > The load by the flask 10 can be dispersed and the load by the plurality of the flasks 10 can be uniformly dispersed throughout the plate 510 by providing the reinforcing portion 560 in the connection portion 540. In the above description, the guide 550 and the reinforcing portion 560 are described as being integrated with the plate 510, but the present invention is not limited thereto. The reinforcing portion 560 may be provided on both sides of the connection portion 540. In order to minimize the weight of the tray 110, the first sub-plate 520 and the second sub-plate 530 are formed in a ring shape so that each of the plates 510 may include a plurality of grooves. In this situation, the plurality of reinforcing portions 560 can prevent warpage of the plate 510 when the flask 10 is placed on the plate 510. [

According to one embodiment of the invention, the incubator 100 may include a sensor portion (not shown). The sensor unit may include a plurality of sensors. A temperature sensor for measuring the level of the liquid contained in the water pan 104, a temperature and humidity sensor for detecting the temperature and humidity in the housing 10, and a sensor for detecting the position of the plate 111 or the flask 10, And a position sensing sensor for sensing the position of the robot.

In addition, the incubator 100 may include environmental control means for controlling the environment in the housing 10 and a processor for controlling the environment control means. The processor can control the environmental control means to create an environment optimized for cell culture based on the values sensed by the water level sensor and the temperature and humidity sensor. The environmental conditioning means may control the temperature and humidity in the housing 10 based on instructions from the processor. The sensor unit and the environmental control means described above are not limited to the above description, and various parameters related to cell culture can be sensed, and adjustment means corresponding to the parameters can be provided.

According to one embodiment of the present invention, the controller 130 may transmit flask information including positional information of the flask 10 obtained from the position sensor to an external device. The flask information may include positional information of the plate 111 on which the flask 10 is mounted, time information of the flask 10, and the like. The external device can store the flask information received from the control unit 130 and can provide the position of the plate 111 and the placed flask 10 to the user based on the flask information.

FIG. 8 is a view illustrating an embodiment in which a flask is transported by a flask handling robot according to an embodiment of the present invention.

 8, the control unit 130 of the incubator 100 may generate information on the flask 10 to be conveyed to the outside, a control signal of the second door 103, and a driving signal of the driving unit 120 . The control unit 130 may control the driving unit 120 to open the second door 103 based on the control signal and the driving signal and to move the flask 10 to a position corresponding to the second door 103 . The driving unit 120 may rotate the tray 110 to move the flask 10 to a position corresponding to the second door 103.

The flask handling robot 620 interlocked with the external device can move to a position corresponding to the second door 103. [ The flask handling robot 620 may be understood as the same or similar concept as the flask handling robot 220 of FIG. According to one embodiment of the present invention, the flask handling robot 620 may have its own control unit and communication unit. Accordingly, the flask handling robot 620 may receive information on the position of the flask to be taken out of the incubator 100. [ The flask handling robot 620 can move up and down to a height at which the flask 10 is located and can transport the flask 10 to the outside of the housing 101 through the second door 103. Unmanned automated cell culture can be performed on the conveyed flask 10 by the unmanned automated cell culture system of FIGS. 1 and 2 described above.

In accordance with the control signal transmission / reception and the movement of the flask handling robot 620, the flask can be returned to the inside of the housing 101 from the outside. Accordingly, the flask 10 can be selectively transported to the inside and outside of the housing 101 by the external device and the flask handling robot 620.

As described above, the driving of the flask handling robot 620 can be minimized as the plate 111 is formed into a circular shape and rotated. For example, when the plate 111 is formed in a polygonal shape and a plurality of flasks are placed on one side, the flask handling robot 620 must perform horizontal movement as well as vertical movement to transport the target flask, The time and space are consumed and an inefficient transportation operation is performed.

According to one embodiment of the present invention, the incubator 100 can mount or transport the flask 10 by various automated robots as well as the flask handling robot 620 described above.

It will be understood by those of ordinary skill in the art that the foregoing description of the embodiments is for illustrative purposes and that those skilled in the art can easily modify the invention without departing from the spirit or essential characteristics thereof. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed in a similar fashion may also be implemented.

The scope of the present invention is defined by the appended claims rather than the detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalents should be interpreted as being included in the scope of the present invention.

10: Flask
100: Cell culture incubator
101: Housing
102: first door
103: Second door
104: Water Fans
110: Tray
111, 510: plate
112: upper cover plate
113: Lower cover plate
114, 511: coupling groove
115: coupling rod
116: Support member
117:
120:
130, 260:
201: Microscope
202: solution reservoir
203: Centrifuge
210: worktable
220, 620: Flask handling robot
230: tube table
240: gripper
250: pipette
270: Cell Counter
520: first sub-plate
530: second sub-plate
540: Connection
550: Guide
560:

Claims (9)

In an unattended automated cell culture system,
An incubator for containing a plurality of flasks for cell culture in multiple layers;
A microscope for observing the culture condition of the cells in the flask;
A workbench capable of placing the flask and performing the operation of collecting the sample from the flask and transferring the solution to the flask for cell culture;
A solution reservoir for storing a plurality of solutions required for cell culture;
A flask handling robot for transferring the flask between the incubator, the microscope and the workbench;
A tube table for placing at least one conical tube capable of receiving a solution necessary for cell and cell culture;
A centrifuge for receiving the conical tube and performing centrifugation for the cells and cell culture in the conical tube;
A gripper for transferring the conical tube between the work table, the tube table and the centrifuge;
A pipette for injecting or collecting a solution necessary for cell and cell culture into the flask or the conical tube; And
A control unit for controlling operations of the flask handling robot, the gripper and the pipette,
, ≪ / RTI &
In the incubator,
housing;
A first door provided on a front surface of the housing;
A second door which is smaller than the first door and is provided on the rear surface of the housing opposite to the front surface of the housing;
A tray positioned within the housing and capable of stacking the plurality of flasks for cell culture in multiple layers; And
And a driving unit positioned outside the housing and coupled to the tray to rotate the tray,
A plurality of plates disposed at regular intervals in the vertical direction and each including a plurality of coupling grooves located at equal intervals; And
And a plurality of coupling rods for coupling the plurality of plates through the coupling grooves of the plurality of plates in the vertical direction,
Wherein the plurality of plates comprises:
A ring-shaped first sub-plate;
A ring-shaped second sub-plate having a diameter smaller than the diameter of the first sub-plate and disposed concentrically with the first sub-plate;
A plurality of connection portions connecting the first sub-plate and the second sub-plate;
A plurality of guides positioned at equal intervals on an upper surface of the first sub-plate and guiding a placement position of the flask; And
And a plurality of reinforcing portions extending from the connecting portion in the downward direction of the incubator to prevent warping of the plate,
The engaging rod passes through the engaging groove of the second sub-plate of the plurality of plates,
The flask is mounted on the connecting portion so that the front end of the flask is placed at an interval between the plurality of engaging rods and the rear end of the flask is placed at an interval between the plurality of guides and is mounted on the connecting portion, Wherein the load by the flask is dispersed.
Unattended automated cell culture system. The method according to claim 1,
The flask handling robot transfers a first flask containing raw material cells from the incubator to the work table,
The pipette injects a first solution for cell separation from the solution reservoir into the first flask,
The flask handling robot shakes the first flask into which the first solution is injected,
The pipette removing the first solution from the first flask,
The pipette injects a second solution for cell separation from the solution reservoir into the first flask,
The flask handling robot transfers the first flask into which the second solution is injected to the incubator so that the raw material cells in the first flask are cultured in the incubator for a preset time,
The flask handling robot transfers the first flask from the incubator to the work table,
The pipette injecting cell culture medium from the solution reservoir into the first flask,
The gripper transfers a first conical tube from the tube table to the work table,
The pipette is obtained by taking a specimen containing the raw material cells from the first flask into which the cell culture medium is injected, injecting the specimen into the first conical tube,
The gripper transfers the first conical tube to the centrifuge, centrifugation is performed on the specimen in the first conical tube,
The gripper transfers the first conical tube from the centrifuge to the work table,
Wherein the pipette removes the upper layer current fluid from the first conical tube,
The pipette reinserting the cell culture medium from the solution reservoir into the first conical tube,
The flask handling robot transfers the second flask, the third flask and the fourth flask from the incubator to the work table,
The pipette injects the cell culture medium from the solution reservoir into the second flask, the third flask and the fourth flask,
The pipette is prepared by uniformly injecting a cell suspension liquid containing the raw material cells from the first conical tube subjected to centrifugal separation into the second flask, the third flask and the fourth flask,
Wherein the flask handling robot transfers the second flask, the third flask and the fourth flask containing the cell suspension liquid to the incubator. 3. The method of claim 2,
The pipette is obtained by taking a specimen of the cell suspensions containing the raw material cells from the first conical tube subjected to centrifugal separation, injecting the specimen into a second conical tube,
The pipette injects a third solution for cell staining into the second conical tube,
The automated unmanned cell culture system,
Further comprising a cell counting device for measuring the number of cells in the specimen,
Wherein the cell counting device measures the number of cells in the specimen in the second conical tube into which the third solution is injected,
Wherein the pipette injects the cell culture medium based on the cell count measured by the cell counting device in injecting the cell culture medium from the solution reservoir into the second flask, the third flask and the fourth flask, , An unattended automated cell culture system. The method of claim 3,
The pipette further injects a cell suspension liquid into the first conical tube subjected to centrifugation,
Wherein the pipette collects the specimen into which the cell suspension fluid is further injected, and injects the specimen into the second conical tube. delete The method according to claim 1,
The tray may include:
An upper cover plate disposed on an uppermost plate of the plurality of plates; And
A lower cover plate disposed below the lowermost plate among the plurality of plates,
/ RTI >
Wherein each of the plurality of plates is formed in a circular shape and a plurality of flasks are placed at regular intervals. The method according to claim 6,
Wherein the plurality of plates, the upper cover plate, and the lower cover plate each include eight coupling grooves located at equal intervals,
The tray may include:
Further comprising eight connecting rods that pass through the eight connecting grooves of the plurality of plates, the upper cover plate, and the lower cover plate in the vertical direction to connect the plurality of plates, the upper cover plate and the lower cover plate An unattended automated cell culture system. delete delete

Images